Design and anticancer mechanism study of a novel 5,8-quinolinedione-o-phenanthroline cobalt(II) complex

doi:10.6023/A26080293

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新型5,8-喹啉二酮-邻菲罗啉钴(II)配合物的设计及抗癌机制研究

周虹宇^a†, 罗富柳^a†, 刘敏栅^a†, 谭明雄^a, 周振^a,*, 梁宏^b, 覃其品^a,b,*

^a玉林师范学院化学与食品科学学院广西农产资源化学与生物技术重点实验室玉林 537000;
^b广西师范大学化学与药学学院桂林 541004

投稿日期:2026-08-19
基金资助:
广西自然科学基金(nos. 2026GXNSFHA00640357, 2026GXNSFHA00640014 and 2025GXNSFAA069961)、国家自然科学基金(no. 22267020)、八桂青年拔尖人才(no. 2024ZKBGQB01)和大学生创新创业训练计划项目(nos. 202510606147, X2026106060034 and X2026106060148)资助项目.

Design and anticancer mechanism study of a novel 5,8-quinolinedione-o-phenanthroline cobalt(II) complex

Zhou Hongyu^a†, Luo Fuliu^a†, Liu Minshan^a†, Tan Mingxiong^a, Zhou Zhen^a,*, Liang Hong^b, Qin Qipin^a,b,*

^aGuangxi Key Laboratory of Agricultural Resources, Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, Yulin 537000;
^bSchool of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004

Received:2026-08-19
Contact: * E-mail: zhouzhen0515@126.com (Z. Zhou); qpqin2018@126.com (Q.-P. Qin).
About author:^†These authors contributed equally to this work.
Supported by:
Natural Science Foundation of Guangxi (nos. 2026GXNSFHA00640357, 2026GXNSFHA00640014 and 2025GXNSFAA069961), the National Natural Science Foundation (no. 22267020), the Bagui Youth top-notch personnel program of Guangxi (no. 2024ZKBGQB01) and the China University Students Innovative Project(nos. 202510606147, X2026106060034 and X2026106060148).

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Abstract

To enhance the anti-cancer efficacy of metal-based drugs, two cobalt(II) complex, [Co(QL’)(phen)(CH₃OH)Cl]·(CH₃OH) (QLCo1) and [Co(QL’)₂(CH₃OH)₂] (QLCo2), were synthesized via coordination of 6,7-dichloro-5,8-quinolinone (QL) and 1,10-phenanthroline (phen) with CoCl₂·6H₂O under controlled conditions. The structures of QL, QLCo1 and QLCo2 were determined by nuclear magnetic resonance (NMR), elemental analysis (ELA), ultraviolet-visible absorption spectroscopy (UV-Vis), infrared spectroscopy (IRS) and mass spectrometry (ESI-MS). In the complexes QLCo1 and QLCo2, the central cobalt(II) atom exhibits a six-coordinated octahedral structure. Additionally, compared with cisplatin (Cis-Pt) and QLCo2, the anti-cancer activity and potential mechanism of the phen-modified cobalt(II) complex QLCo1 were investigated. Compared with normal liver cells (HL-7702, AML12), human cervical cancer cells (HeLa), and human lung cancer cells (A549), QLCo1 exhibited better inhibitory effects on human lung cancer cisplatin-resistant cells (A549/CDDP), with an IC₅₀ value of 0.30±0.02 μmol/L; this potency was markedly superior to Cis-Pt (67.2 ± 1.3 μmol/L), QL (>100.0 μmol/L), CoCl₂·6H₂O(>100.0 μmol/L), phen (>100.0 μmol/L) and QLCo2 (IC₅₀= 4.0±0.8 μmol/L), respectively. Flow cytometry, Western blotting experiments, cell uptake and immunofluorescence experiments revealed showed that QLCo1 and QLCo2 induced apoptosis in A549/CDDP cells, with apoptosis rates of 46.45% and 44.17%, respectively. Complexes QLCo1 and QLCo2 mediated endogenous apoptosis in A549/CDDP cancer cells through the mitophagy pathway, indicating that phen enhanced the ability of the cobalt(II) complex QLCo2 to induce apoptosis in A549/CDDP cancer cells. From the cobalt uptake assay, complex QLCo1 exhibited obvious priority on the cell uptake effect than QLCo2, which should should be undoubtedly correlated with the key roles of the phen ligand of QLCo1. Moreover, QLCo1 could significantly inhibit the growth of A549/CDDP solid tumors, with an inhibition rate of 50.6%, which was markedly higher than that of Cis-Pt (ca. 26.6%). In conclusion, this study has identified a 6,7-dichloro-5,8-quinolinone dithiocarbamate complex, named QLCo1, which can effectively induce apoptosis in A549/CDDP cancer cells through mitochondrial autophagy.

Key words: Cobalt(II) complex, 6,7-dichloro-5,8-quinolinedione, mitophagy

Cite this article

Zhou Hongyu, Luo Fuliu, Liu Minshan, Tan Mingxiong, Zhou Zhen, Liang Hong, Qin Qipin. Design and anticancer mechanism study of a novel 5,8-quinolinedione-o-phenanthroline cobalt(II) complex[J]. Acta Chimica Sinica, doi: 10.6023/A26080293.

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新型5,8-喹啉二酮-邻菲罗啉钴(II)配合物的设计及抗癌机制研究

Design and anticancer mechanism study of a novel 5,8-quinolinedione-o-phenanthroline cobalt(II) complex

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